The objectives of this project will be to prepare potential therapeutic agents for cardiovascular disease. The compounds to be synthesized will be based on current concepts dealing with feedback control and other intracellular regulatroy mechanisms. In feedback control a terminal metabolite serves to inhibit an enzymatic transformation occuring early in the metabolic sequence. Current evidence indicates that the terminal metabolite causes inhibition by binding at an enzymatic site separate from the active site for the substrate, and this other site has been termed the allosteric site. In this study, structural analogs of inhibitory metabolites or allosteric effectors for hydroxymethyl glutarate reductase and tyrosine hydroxylase will be synthesized. Such specially designed analogs may simulate the terminal metabolites in the feedback control mechanisms and prove to be effective regulators of cholesterol and catecholamine biosynthesis.